Myeloid derived suppressor cells (MDSCs) expand in cancer bearing hosts and contribute to tumor immune evasion. M2 macrophages constitute a major cellular component of cancer-related inflammation. However, the correlation between circulating MDSCs and infiltrating M2 macrophages in tumor tissues from patients with esophageal cancer (ECA), and its potential relationship with the polarization of Th2 cells remain unclear. In the present study, we showed the level of MDSCs in PBMC and Arg1 in plasma were significantly elevated in ECA patients, and the increased ratio of MDSC in PBMC was closely related to the expression of CD163 in cancer tissues. In addition, the ECA patients exhibited remarkable increases in the mRNA levels of IL-4 and GATA3, as well as the protein levels of IL-13 and IL-6, but IFN-γ and IL-12 in peripheral blood were decreased. Our data indicate that the increased Th2 cytokines are associated with MDSCs and M2 macrophages polarization, and foster the infiltration of CD163+M2 macrophages in cancer tissues, which promote the formation of immunosuppressive microenvironment in ECA patients.

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Upregulated high-mobility group box 1 (HMGB1) has been found in many diseases. Nevertheless, the function of HMGB1 on modulating the proliferation of lung cancer cells (Lewis cells) and inhibiting apoptosis is poorly understood, as well as the involved intracellular signalling. In the present study, we firstly found the apoptosis of Lewis was increased following Hanks' balanced salt solution (HBSS)-induced starvation, while it was rescued after exogenous HMGB1 protein was added; furthermore, the receptor for advanced glycation end products (RAGE) and Toll-like receptor (TLR4) could coordinately improve the proliferation of tumour cells in vitro, and HMGB1 could enhance the phosphorylation of PI3K/Akt and Erk1/2, inhibit the expression of pro-apoptosis protein Bax and promote the expression of anti-apoptosis protein Bcl-2. These findings clearly demonstrated that HMGB1-RAGE/TLR4-PI3K-Akt/Erk1/2 pathway contributed to the proliferation of Lewis. Moreover, our observations provide experimental and theoretical basis for clinical biological therapy for cancers; it also may be a new target for intervention and treatment of lung cancer.

BACKGROUND: Cervical cancer is one of the most common cancers in women worldwide, often associated with the infection of human papillomavirus (HPV). Toll-like receptor 8 (TLR8), a pattern recognition receptor, is involved in viral nucleic acid sensing. Recently TLR8 has been shown to be expressed in cancer cells, and it has been suggested that it may help cancer cell growth and tumor development. The objective of this study is to investigate the expression of TLR8 expression and its relationship with Bcl-2 and VEGF in cervical cancer cells.METHODOLOGY/PRINCIPAL: The mRNA expression levels of Bcl-2, VEGF and TLR-7,-8,-9 in newly diagnosed cervical cancer patients were detected by quantitative real-time PCR (qRT- PCR). Epifluorescence microscope was used to determine the presence of TLR8 protein in Hela cells. The cell cycle and apoptosis were analyzed by flow cytometer, and the cell proliferation was measured by MTT assay. Our data showed the increased mRNA levels of TLR8 in human cervical cancer samples as well as in HeLa cells, a cell line derived from a human cervical cancer. In addition, there was a positive correlation between the expression levels of TLR8 and Bcl-2 and VEGF in cervical cancer patients. When Hela cells were treated with TLR8 agonist CL075, the percentage of cells in G2/M +S was remarkably increased, accompanied by increased COX-2, BCL-2 and VEGF mRNA levels.CONCLUSIONS/SIGNIFICANCE: The mRNA expression level of TLR8 in the patients with cervical cancer and Hela cells were up-regulated, it consistent with the increased expression of VEGF and Bcl-2. The results suggest that TLR8 may be an interesting therapeutic target in cervical cancer.

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Mesenchymal stem cells are important cells in tumor microenvironment. We have previously demonstrated that IL-17B/IL-17RB signal promoted progression of gastric cancer. In this study, we further explored the effect of IL-17B on mesenchymal stem cells in tumor microenvironment and its impact on the tumor progression. The results showed that IL-17B induced the expression of stemness-related genes Nanog, Sox2, and Oct4 in mesenchymal stem cells and enhanced its tumor-promoting effect. The supernatant from cultured mesenchymal stem cells after treating with exogenous rIL-17B promoted the proliferation and migration of MGC-803, therefor suggesting that rIL-17B might promote mesenchymal stem cells to produce soluble factors. In addition, rIL-17B also activated the NF-κΒ, STAT3, β-catenin pathway in mesenchymal stem cells. Our data revealed a new mechanism that IL-17B enhanced the progression of gastric cancer by activating mesenchymal stem cells.

β-Lactam-resistant Klebsiella isolates continue to cause multidrug resistance infections worldwide. This study aimed to describe the geographical distribution of extended spectrum β-lactamase (ESBL), AmpC β-lactamase (AmpC), and carbapenemase production among 139 Klebsiella isolates recovered from patients at major referral health facilities in Ghana. The phenotypic methods of combined disc diffusion test, modified three-dimensional test, modified Hodge test (MHT), and combined disc test were performed for each isolate to detect ESBL, AmpC, carbapenemase, and metallo-β-lactamase (MBL) producers, respectively. Except for MBL, all other β-lactam resistance mechanisms were highest in the healthcare facilities situated in the northern belt of Ghana. Significant regional difference of ESBL producers was observed between the northern and middle belts as well as the northern and southern belts. Genotypic detection with polymerase chain reaction (PCR) revealed the presence of bla TEM 36/139 (25.9%), bla SHV 40/139 (28.8%), bla CTX-M 37/139 (26.6%), bla OXA-48 3/139 (2.16%), and bla NDM 1/139 (0.72%) genotypes. In conclusion, there were variations in β-lactam resistance among Klebsiella spp. from health facilities situated in the northern, middle, and southern belts of Ghana. The study provides preliminary evidence that emphasizes the need to direct more attention to antimicrobial resistance control, especially in the northern belt of Ghana. Findings from this study may be critical for creating and fine-tuning effective antimicrobial resistance control strategies and for informing accurate antibiotic prescription by practitioners.

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